Hypertension [JOURNAL]
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200 papers
Association Between Postprandial Hypotension Determined by Ambulatory Blood Pressure Monitoring and Falls Among Older Adults With Hypertension Who Are Taking Antihypertensive Medication: Results From the AMBROSIA Study.
Narita K, Bowling CB, Cannavale K … +9 more , Fang C, Harrison TN, Muntner P, Qian L, Schwartz JE, Sim JJ, Wei R, Reynolds K, Shimbo D
Hypertension · 2026 Apr · PMID 41641534 · Publisher ↗
BACKGROUND: Postprandial hypotension (PPH) may contribute to falls among older adults, particularly those taking antihypertensive medication. However, evidence on this association in community-dwelling populations is lim...
BACKGROUND: Postprandial hypotension (PPH) may contribute to falls among older adults, particularly those taking antihypertensive medication. However, evidence on this association in community-dwelling populations is limited. Since ambulatory blood pressure (BP) monitoring captures BP during daily activities, it may provide accurate assessments of PPH outside the clinic setting. METHODS: This prospective cohort study examined the association between PPH and fall risk among community-dwelling adults aged ≥65 years taking antihypertensive medication. At baseline, participants underwent 24-hour ambulatory BP monitoring; subsequently, they completed monthly fall calendars during a 12-month follow-up. PPH by systolic BP (SBP; systolic PPH) was defined as a postprandial SBP decline, mean SBP during the hour before the meal minus the minimum SBP during the 2 hours after the meal, following any meal of ≥20 mm Hg, or a decrease to SBP ≤90 mm Hg when preprandial SBP was ≥100 mm Hg. RESULTS: Among 626 participants (mean±SD age, 74.6±6.2 years; 56.1% women), 442 (70.6%) experienced systolic PPH. The mean±SD number of meals was 2.6±0.8 during the ambulatory BP monitoring period. During the 12-month follow-up, falls occurred in 169 of 442 (38.2%) participants with systolic PPH and 70 of 184 (38.0%) participants without systolic PPH. Systolic PPH was not associated with fall risk (adjusted hazard ratio, 0.93 [95% CI, 0.69-1.26]). A restricted cubic spline analysis demonstrated no evidence of an association between the largest postprandial SBP decline across all meals and fall risk. CONCLUSIONS: In this cohort study, PPH identified by ambulatory BP monitoring was common but not associated with risk of falls.
Sex-Specific Blood Pressure and Brain Microvascular Traits in a Model of Low-Renin Hypertension.
De Silva TM, Sabharwal R, Gerhold TD … +3 more , Lynch CM, Baumbach GL, Faraci FM
Hypertension · 2026 Jun · PMID 41641533 · Full text
BACKGROUND: Hypertension is a leading risk factor for negative health outcomes due to end-organ effects that include small vessel disease in the brain. Low-renin hypertension is understudied at the blood pressure (BP), m...
BACKGROUND: Hypertension is a leading risk factor for negative health outcomes due to end-organ effects that include small vessel disease in the brain. Low-renin hypertension is understudied at the blood pressure (BP), microvascular, and mechanistic level, and in relation to biological sex. This study examined the effects of low-renin hypertension, produced by activation of the brain renin-angiotensin system in a deoxycorticosterone acetate (DOCA) salt model. METHODS: C57BL/6J mice were treated with DOCA (or sham) and given tap HO and HO with 0.15 mol/L NaCl for 3 to 4 weeks followed by assessment of the microvasculature. Mean arterial pressure and BP variability were measured using radiotelemetry. RESULTS: Baseline and diurnal changes in mean arterial pressure, increases in mean arterial pressure, and BP variability during DOCA salt, were greater in male than female mice. Compared with sham treatment, endothelial function of cerebral arterioles in vivo was reduced by >70% by DOCA salt in males, dysfunction that could be reversed by local inhibition of AT1R (angiotensin II type 1 receptor), MR (mineralocorticoid receptor), or Rho kinase. DOCA salt increased arteriolar cross-sectional area and wall stiffness in male, but not female mice. In males (but not females), performance on a novel object recognition test was selectively impaired. CONCLUSIONS: Activation of the central renin-angiotensin system has sex-specific effects on BP, diurnal changes in BP, BP variability, arteriolar structure, and stiffness. Marked endothelial dysfunction was present in males (with several contributing mechanisms). These findings provide new insight into BP-related and small vessel disease-related phenotypes, mechanisms that contribute to endothelial dysfunction, and sex-specific differences in BP traits in a preclinical model of low-renin hypertension.
Concordant and Discordant Transcriptomic Signatures of Twin Placentas in the Setting of Preeclampsia.
Ackerman WE, Buhimschi IA, Jing H … +3 more , Brown TL, Zhao G, Buhimschi CS
Hypertension · 2026 Jun · PMID 41641529 · Full text
BACKGROUND: Multifetal pregnancies have increased preeclampsia risk, but the underlying pathogenesis may differ from that of singletons. It remains unclear whether twin placentas show molecular signs of preeclampsia sync...
BACKGROUND: Multifetal pregnancies have increased preeclampsia risk, but the underlying pathogenesis may differ from that of singletons. It remains unclear whether twin placentas show molecular signs of preeclampsia synchronously. METHODS: We performed RNA sequencing on 32 individual placental samples from twin gestations grouped by preeclampsia status: 24 dichorionic twin (DT) and 8 monochorionic twin gestations. Ten singleton placentas from preeclamptic pregnancies were also analyzed. A benchmark data set (GSE203507, GSE114691, and GSE1482410) and a test data set (GSE190973) comprised 71 early onset preeclampsia and 69 control singleton placentas. Differential abundance analysis was conducted, and machine learning was used to derive a novel 98-transcript classification signature (accuracy >0.97 in benchmark and test data sets). RESULTS: Across 7 groups, 2946 transcripts were differentially modulated (likelihood-ratio test; false discovery rate <0.05). Placental signature scoring distinguished normotensive from early onset preeclampsia in GSE203507 singletons (<0.0001) although normotensive DTs did not differ from DTs with preeclampsia (Kruskal-Wallis/Dunn). Notably, some twin placentas without clinical preeclampsia exhibited preeclampsia-like profiles. Linear mixed-effects regression, which accounted for intertwin correlation structure, revealed increasing signature scores across singleton and DT groups (all <0.01): normotensive singletons<normotensive DT<DT with preeclampsia<singletons with preeclampsia. Functional analysis in twins showed preeclampsia-like dysregulation but with pronounced variability. Intertwin divergence was more prominent in DT than in monochorionic twin samples, regardless of clinical diagnosis. CONCLUSIONS: These findings highlight the complexity of preeclampsia pathology in twins. In DT pregnancies complicated by preeclampsia, placental involvement may be asymmetrical, suggesting that disease may arise from a single affected placenta; however, these results require replication.
C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis.
Moyes AJ, Sand C, Young L … +8 more , Pérez-Ternero C, Salam AT, Baliga RS, Mohammad S, Antcliffe DB, Gordon AC, Aubdool AA, Hobbs AJ
Hypertension · 2026 Jun · PMID 41636071 · Full text
BACKGROUND: Sepsis is a life-threatening condition and a major cause of mortality in intensive care units worldwide, a clear unmet medical need. CNP (C-type natriuretic peptide) regulates inflammation and cardiovascular...
BACKGROUND: Sepsis is a life-threatening condition and a major cause of mortality in intensive care units worldwide, a clear unmet medical need. CNP (C-type natriuretic peptide) regulates inflammation and cardiovascular homeostasis, but its involvement in sepsis pathogenesis is not fully elucidated. This study investigated the intrinsic role of CNP, and therapeutic potential of the peptide, in offsetting the pathogenesis of sepsis. METHODS: Plasma concentrations of CNP, and its N-terminal cleavage product NT-proCNP (N-terminal pro-CNP), were measured in sepsis patients. Cardiac function, vascular hemodynamics, endothelial integrity, and biomarkers of inflammation were analyzed in wild-type, endothelium-restricted (ecCNP), or cardiomyocyte-restricted (cmCNP) CNP knockout animals, or global NPR (natriuretic peptide receptor)-C deficient mice, in etiologically distinct models of sepsis. CNP (0.2 mg/kg per d) was infused to rescue any adverse phenotype and probe therapeutic potential. RESULTS: Circulating [NT-proCNP] increased in sepsis patients and was associated with reduced disease severity. ecCNP mice exhibited an aggravated phenotype compared with wild-type mice in experimental sepsis, exemplified by impaired microcirculatory flow, edema, and increased expression of inflammatory biomarkers. In addition, cmCNP animals showed overt cardiac dysfunction following lipopolysaccharide treatment. This worsened phenotype was mirrored in NPR-C mice, implying that this cognate NPR subtype underpins the salutary actions of endogenous CNP. Pharmacological CNP administration improved microvascular perfusion, cardiac output, and inflammation in wild-type and ecCNP, but not NPR-C, mice. CONCLUSIONS: Endogenous CNP plays a protective role in sepsis by preserving microvascular perfusion, reducing inflammation, maintaining endothelial integrity, and sustaining cardiac function via NPR-C. Pharmacologically targeting CNP signaling warrants further evaluation as a potential therapeutic opportunity in sepsis.
Loss of ROR2 Tyrosine Kinase Receptor Is Associated With Endothelial Dysfunction in PAH via Inappropriate Integrin β1 Activation.
Mitra A, Agarwal S, Chakraborty A … +20 more , Zhong BL, Heo L, Roy A, Bankar A, Pacheco A, Auer N, Dunn A, Chelladurai P, Jain A, Matos Muñoz JA, Guardado ES, Yi D, Zhao H, Man KWD, Nair R, Hong J, Kuebler WM, Guenat OT, Dai Z, de Jesus Perez VA
Hypertension · 2026 Apr · PMID 41636059 · Full text
BACKGROUND: Endothelial dysfunction is a key feature of pulmonary arterial hypertension (PAH). Previously, we demonstrated decreased Wnt7a transcript levels, causing reduced angiogenesis in PAH. Wnt7a expression correlat...
BACKGROUND: Endothelial dysfunction is a key feature of pulmonary arterial hypertension (PAH). Previously, we demonstrated decreased Wnt7a transcript levels, causing reduced angiogenesis in PAH. Wnt7a expression correlates with tip formation via ROR2 (receptor tyrosine kinase-like orphan receptor 2), a tyrosine kinase receptor. We hypothesized that ROR2 activation in pulmonary microvascular endothelial cells (PMVECs) promotes angiogenesis, particularly endothelial barrier establishment, and its loss causes PAH. METHODS: Endothelial-specific ROR2 knockout (ROR2 ECKO) and wild-type mice were studied under normoxia and chronic hypoxia using echocardiography, hemodynamics, and lung morphometry. PMVECs from healthy and PAH lungs were transfected with ROR2 siRNA/constructs for functional and molecular studies. Focal adhesion activation and force generation were assessed via Förster resonance energy transfer-based methods. Bulk and single-cell transcriptomic analyses were performed on siROR2 (ROR2 siRNA) PMVECs and ROR2 ECKO lungs. RESULTS: ROR2 ECKO mice exacerbated pulmonary hypertension and vascular remodeling in hypoxia. Single-cell RNA-sequencing of lung endothelial cells revealed dysregulated barrier formation and angiogenesis. Evans blue dye extravasation confirmed reduced endothelial barrier integrity in ROR2 ECKO mice. ROR2-deficient PAH PMVECs displayed increased adhesion, permeability, and focal adhesion numbers, with reduced VE-cadherin at cell junctions. Confocal imaging and foster resonance energy transfer revealed ROR2 localization in focal adhesions, interacting with ITGB1 (integrin β1) which remained in an active, adhesion-promoting state in ROR2-deficient cells. Restoring ROR2 in PAH PMVECs normalized adhesion, barrier function, and focal adhesion abundance. Transcriptomic analysis revealed Rab12 mediated ROR2-ITGB1 crosstalk, whose knockdown mimicked ROR2 deficiency in PMVECs. CONCLUSIONS: ROR2 regulates pulmonary angiogenesis by maintaining endothelial barrier integrity and facilitating integrin recycling. ROR2 restoration could be a potential therapeutic approach for PAH.
Endothelial LRRC8C Associates With LRRC8A and LRRC8B to Regulate Vascular Reactivity and Blood Pressure.
Yu Q, Zhao Y, Maurer J … +8 more , Arullampalam P, John N, Tranter JD, Abd El-Aziz TM, Rahimi M, Lin M, Halabi CM, Sah R
Hypertension · 2026 Apr · PMID 41636028 · Full text
BACKGROUND: Endothelial mechanosensing is essential for controlling vascular tone. LRRC8A (leucine-rich repeat-containing protein 8A) was previously identified as a core subunit of the mechanoresponsive LRRC8 complex, fu...
BACKGROUND: Endothelial mechanosensing is essential for controlling vascular tone. LRRC8A (leucine-rich repeat-containing protein 8A) was previously identified as a core subunit of the mechanoresponsive LRRC8 complex, functionally encoding the endothelial volume regulatory anion channel and regulating vascular function. This study aims to identify the molecular identity of the endothelial LRRC8 complex and its function in vascular reactivity and blood pressure control. METHODS: We generated germline epitope-tagged -3xFlag knock-in mice and endothelium-specific -3xFlag overexpression mice to permit LRRC8A and LRRC8C immunoprecipitation and define LRRC8 subunit interactions. We combined in vivo and in vitro loss-of-function models, electrophysiology, immunoblotting, and pressure myography of third-order mesenteric arteries to examine the contributions of individual LRRC8A/B/C subunits to vascular function and underlying signaling pathways. The contributions of LRRC8C to blood pressure control in vivo were further assessed using the angiotensin-induced hypertension model in knockout mice. RESULTS: Although all LRRC8A-E subunits are expressed in endothelium, co-immunoprecipitation revealed enrichment of LRRC8A/B/C, suggesting the existence of an endothelial LRRC8A/B/C heteromer. depletion studies showed codependent expression of LRRC8A/B/C, but not LRRC8D. Only LRRC8A and LRRC8C deficiency impaired AKT and endothelial NO synthase phosphorylation, increased myogenic tone (2.2- and 1.9-fold increase, respectively), and reduced endothelial NO synthase-dependent vasodilation (45% and 61% reduction, respectively). Global Lrrc8c knockout mice phenocopied Lrrc8a knockouts and exhibited exacerbated angiotensin-induced hypertension, as evidenced by 15% increase in mean arterial pressure. CONCLUSIONS: LRRC8A/B/C form the endothelial LRRC8 heteromeric complex. LRRC8C is nonredundant in supporting endothelial AKT-endothelial NO synthase signaling, vascular relaxation, and resistance to hypertension.
Bacterial Extracellular Vesicles Mediate Microbiota-Host Communication to Regulate Blood Pressure in Male Rats.
Shi H, Shi F, Wagle R … +6 more , Gonzalez-Gonzalez MA, Mell B, Oliver B, Zhu T, Joe B, Durgan DJ
Hypertension · 2026 Apr · PMID 41636025 · Full text
BACKGROUND: Altered gut microbiota composition has been implicated in the development of hypertension. Evidence suggests bacterial products and metabolites can enter circulation, act on peripheral tissues, and modulate b...
BACKGROUND: Altered gut microbiota composition has been implicated in the development of hypertension. Evidence suggests bacterial products and metabolites can enter circulation, act on peripheral tissues, and modulate blood pressure (BP). We identified extracellular vesicles (EVs) of bacterial origin (bacterial extracellular vesicles [bEVs]) in the circulation of spontaneously hypertensive stroke-prone rats (SHRSP). We hypothesized that bEVs mediate communication between microbiota and the host, and that bEVs from SHRSP microbiota contain unique cargo that promotes hypertension. METHODS: EVs were isolated from plasma and cecal content of SHRSP and Wistar-Kyoto (WKY) rats. Multiomics analysis, including 16S rRNA sequencing, small RNA sequencing, lipidomics, and proteomics were performed to assess the cargo of bEVs. BEVs from WKY and SHRSP were transplanted by oral gavage to WKY and SHRSP recipients, and the effects on BP and sympathetic activity were monitored. The potential role of bEVs on BP was also evaluated in Dahl salt sensitive (S) and obstructive sleep apnea models of hypertension. RESULTS: Significant differences were observed in WKY and SHRSP bEV cargo, including small RNAs, proteins, and PAMPs (pathogen-associated molecular patterns). Transplantation of SHRSP bEVs to WKY rats increased renal sympathetic nerve activity and elevated BP. Moreover, we showed that bEVs influence BP regulation in Dahl S and obstructive sleep apnea-induced hypertension. CONCLUSIONS: Our findings position bEVs as critical mediators of microbiota-host communication in BP regulation and demonstrate that bEVs from the altered SHRSP microbiota promote hypertension. Our findings shed new light on the role of bEVs in hypertension pathogenesis and offer new perspectives for diagnostics and therapeutic interventions.
Determinants of Placental Versus Maternal Preeclampsia.
Aisagbonhi O, Jacobs MB, Meads M … +6 more , Stanley V, Lamale-Smith LM, Emeruwa UN, Laurent LC, Fisch KM, Horii M
Hypertension · 2026 Apr · PMID 41636024 · Full text
BACKGROUND: The placenta is known to be critical in the etiology of preeclampsia. However, there is a subset of preeclampsia cases without identifiable placental pathology. We evaluated which clinical preeclampsia classi...
BACKGROUND: The placenta is known to be critical in the etiology of preeclampsia. However, there is a subset of preeclampsia cases without identifiable placental pathology. We evaluated which clinical preeclampsia classification system best distinguishes preeclampsia with placental pathology from preeclampsia without placental pathology. METHODS: We evaluated 5 placental pathological features in 197 placentas from patients with preeclampsia grouped by 3 clinical preeclampsia subclasses: (1) preeclampsia with calculated infant birthweight <10th percentile for gestational age (small for gestational age [SGA] preeclampsia) versus preeclampsia with birthweight ≥10th percentile for gestational age (not SGA preeclampsia); (2) preeclampsia with delivery before 34 weeks of gestation (early delivery preeclampsia) versus preeclampsia with delivery at or after 34 weeks of gestation (late delivery preeclampsia); and (3) preeclampsia with severe features versus preeclampsia without severe features. Clinical, histological and molecular findings in patients with preeclampsia were compared with normotensive patients, with and without SGA infants (N=1078 total). RESULTS: The SGA versus not small for gestational age preeclampsia classification system performed best (likelihood ratios [95% CI] for ≥3 of 5 placental pathological findings: 15.7 [6.5-38.1] in SGA preeclampsia versus not small for gestational age preeclampsia; 6.8 [4.3-10.8] in early delivery preeclampsia versus late delivery preeclampsia; and 5.2 [1.95-14.1] in preeclampsia with severe features versus preeclampsia without severe features; all <0.0001). SGA preeclampsia and SGA normotensive placentas were abnormal and shared alterations in hypoxia, TNFα (tumor necrosis factor alpha), glycolysis, unfolded protein response, estrogen response, ultraviolet response, p53, TGFβ (transforming growth factor beta), and mTORC1 (mammalian target of rapamycin complex 1) signaling pathways. CONCLUSIONS: Classifying preeclampsia based on birthweight percentile for gestational age is the most useful system for consistently identifying preeclampsia associated with placental pathology.
Galectin-1 Is a Marker but Not a Mediator of Heart Failure With Preserved Ejection Fraction.
Wassenaar JW, Smart CD, Fehrenbach DJ … +12 more , Shuey MM, Sangowdar P, Zhong L, Miller FJ, Wells QS, Huang S, Collins SP, Storrow AB, Miller KF, Gupta DK, Doran AC, Madhur MS
Hypertension · 2026 Apr · PMID 41614247 · Full text
BACKGROUND: The immune system is emerging as a key player in driving cardiac remodeling in heart failure with preserved ejection fraction (HFpEF). Galectin-1 () is a carbohydrate-binding protein that we previously identi...
BACKGROUND: The immune system is emerging as a key player in driving cardiac remodeling in heart failure with preserved ejection fraction (HFpEF). Galectin-1 () is a carbohydrate-binding protein that we previously identified as being upregulated in cardiac myeloid cells in a preclinical model of HFpEF. Our objective was to determine the role of galectin-1 in HFpEF in both preclinical models and clinical cohort studies. METHODS: Galectin-1 was measured using the Olink proximity extension assay in human cohorts. HFpEF was induced in mice with myeloid-specific and global deletion of galectin-1 and corresponding controls using the hypertensive deoxycorticosterone acetate-salt model. RESULTS: Plasma galectin-1 was higher in both a preclinical model of HFpEF (=0.022) and in patients with heart failure (<0.001) in the UK Biobank. In patients without heart failure, higher galectin-1 levels were associated with a greater risk for incident heart failure (hazard ratio, 3.1 for quartile 4 versus quartile 1; <0.001). In patients with acute HFpEF, galectin-1 was positively associated with NT-proBNP (N-terminal pro-B-type natriuretic peptide), a biomarker of worse prognosis (ordinal regression <0.001). Mice with myeloid cell or global deficiency of galectin-1, however, exhibit no difference in deoxycorticosterone acetate-salt-induced HFpEF. CONCLUSIONS: Greater circulating galectin-1 levels are associated with a higher risk of incident heart failure and higher NT-proBNP among patients with acute HFpEF. However, neither global nor myeloid deficiency of galectin-1 altered the cardiovascular phenotype in a preclinical model of HFpEF, suggesting that it is a marker but not a causal mediator of the disease.
Abnormal Pro-inflammatory Immune Cell Responses Precede Clinical Onset of Hypertensive Disorders of Pregnancy.
Rezk A, DeBolt CA, Breville G … +6 more , Li R, Riis VA, Ncube L, Barry F, Elovitz MA, Bar-Or A
Hypertension · 2026 Apr · PMID 41608786 · Full text
BACKGROUND: Hypertensive disorders of pregnancy (HDP) are significant contributors to maternal morbidity and mortality, as well as to long-term cardiovascular health, with an inequitable burden among Black individuals. W...
BACKGROUND: Hypertensive disorders of pregnancy (HDP) are significant contributors to maternal morbidity and mortality, as well as to long-term cardiovascular health, with an inequitable burden among Black individuals. While there is growing interest in the possibility that inflammatory responses are involved with HDP, work to date has primarily been cross-sectional, and immune cell profiling has focused on cell phenotyping that may not capture relevant functional properties of the immune cells. METHODS: We examined whether an abnormal inflammatory cellular profile is found in the blood of Black pregnant women before the clinical onset of HDP. This nested case-control study included 27 pregnant women who later developed HDP and 73 who had a healthy pregnancy delivered at term, all of whom provided blood samples during the second trimester. Phenotype and function of immune cell populations were examined by multi-parametric flow cytometry. RESULTS: We observed a greater abundance of peripheral blood T cells in individuals later diagnosed with HDP. Among these were CD161 CD4 T cells that showed increased expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF). Similarly, monocytes from these individuals exhibited increased expression of pro-inflammatory cytokines. Anti-inflammatory T cells and monocytes were not altered in those with versus without a future diagnosis of HDP. CONCLUSIONS: We identify a pro-inflammatory cellular immune signature in pregnant individuals destined to have HDP. Immune signatures may serve as a new biomarker to identify subsets of individuals at particular risk for HDP and point to new therapeutic targets to prevent HDP.
Iron Overload-Induced Ferroptosis Drives Placental Dysfunction in Preeclampsia.
Yang Y, Zuo H, Ma X … +7 more , Chen W, Sun M, Xiang Q, Wei Y, Zhao Y, Qi H, Liu T
Hypertension · 2026 Jul · PMID 41608783 · Publisher ↗
BACKGROUND: Preeclampsia, a life-threatening hypertensive disorder of pregnancy, has been linked to iron dysregulation, though mechanistic insights remain limited. METHODS: We integrated clinical data, a reduced uterine...
BACKGROUND: Preeclampsia, a life-threatening hypertensive disorder of pregnancy, has been linked to iron dysregulation, though mechanistic insights remain limited. METHODS: We integrated clinical data, a reduced uterine perfusion pressure mouse model, in vitro trophoblast cell experiments, and placental organoids derived from patients with preeclampsia. Iron metabolism was assessed via mass spectrometry, quantitative polymerase chain reaction, Peris' Prussian blue staining and immunohistochemistry. Ferroptosis markers and iron transporters were analyzed. Interventions included the iron chelator deferoxamine, antioxidant MitoQ, ferroptosis inhibitor Fer-1 (ferrostatin-1), and the apoptosis inhibitor Z-VAD. RESULTS: Patients with preeclampsia exhibited elevated hemoglobin, ferritin, and serum iron levels from the second trimester, alongside placental iron overload. Single-cell/nucleus RNA sequencing revealed dysregulated iron transporters (↑, ↑, ↓) in preeclampsia trophoblasts. Iron overload induced ferroptosis and apoptosis in trophoblasts, evidenced by increased lipid peroxidation (4HNE↑, Gpx4↓), ROS, Tunnel staining positive and cell death, while suppressing PlGF and progesterone secretion. Both deferoxamine and MitoQ rescued these effects in vitro (similar to Ferr-1) and in preeclampsia-derived organoids. The reduced uterine perfusion pressure model confirmed the preservation of iron dyshomeostasis and ferroptosis in preeclamptic placentas, while oral administration of MitoQ was found to reduce 4-hydroxynonenal and malondialdehyde expression in placenta. CONCLUSIONS: Our findings reveal that iron overload and subsequent ferroptosis contribute to placental damage in preeclampsia, suggesting that iron metabolism dysregulation is a critical feature of the disease. This highlights the need to reevaluate iron supplementation protocols in high-risk pregnancies and to consider individualized iron management strategies that balance maternal-fetal iron requirements while minimizing oxidative stress.
Hypertension in Patients With End-Stage Kidney Disease Requiring Dialysis: Bridging the Divide Between Evidence and Practice.
Mayeda L, Bansal N
Hypertension · 2026 Mar · PMID 41603034 · Full text
Hypertension is a highly prevalent and modifiable risk factor, affecting >80% of patients undergoing dialysis. Its pathophysiology is complex and differs from that of the general population, driven by factors such as vol...
Hypertension is a highly prevalent and modifiable risk factor, affecting >80% of patients undergoing dialysis. Its pathophysiology is complex and differs from that of the general population, driven by factors such as volume overload, arterial stiffness, overactivation of the sympathetic and renin-angiotensin-aldosterone systems, and endothelial dysfunction. Achieving optimal blood pressure and volume control is central to dialysis care, with significant implications for cardiovascular outcomes and patient quality of life. Despite its importance, evidence guiding hypertension management in this population remains limited. Furthermore, reliable, objective methods to assess extracellular volume are lacking. This review examines current approaches to the assessment and management of hypertension in maintenance hemodialysis, summarizing existing evidence, clinical guidelines, and ongoing challenges in blood pressure and volume control.
Estimating the Potential Impact of the 2024 UK Salt Reduction Targets on Cardiovascular Health Outcomes and Health Care Costs in Adults: A Modeling Study.
Bandy L, Amies-Cull B, Luick M … +3 more , Cobiac LJ, Jebb SA, Scarborough P
Hypertension · 2026 Mar · PMID 41582820 · Full text
BACKGROUND: Excessive sodium intake is responsible for 3 million deaths a year globally. The UK is one of 64 countries to have a salt reduction program to help reduce the population's sodium intake. It is a voluntary sch...
BACKGROUND: Excessive sodium intake is responsible for 3 million deaths a year globally. The UK is one of 64 countries to have a salt reduction program to help reduce the population's sodium intake. It is a voluntary scheme with 108 category-specific salt content targets for the grocery and out-of-home sectors. This study aimed to estimate the potential impact of the 2024 targets on cardiovascular outcomes and health care costs for UK adults. METHODS: Long-term health modeling was based on the adult population in England. Changes in salt intake (g/d), whether the targets were met, were estimated using consumption data from the National Diet and Nutrition Survey 2018/19. Impact on ischemic heart disease and stroke, quality-adjusted life years, and health care costs were estimated using PRIMEtime, a proportional multistate life table model. RESULTS: If the salt reduction targets set for 2024 had been met, then salt intake would have reduced from 6.06 g/d (95% CI, 5.18-6.31) to 4.94 g/d (4.73-5.15), a reduction of 1.12 g/d (1.05-1.20). This would lead to 103 000 (UI, 41 000-161 000) fewer cases of ischemic heart disease and 25 000 (10 000-39 000) fewer cases of stroke over 20 years. A modeled 243 000 (94 000-383 000) quality-adjusted life years would be saved with a net saving of £1.00 billion (£0.35-1.73 billion) to the National Health Service over the remaining lifetime of the adult population. CONCLUSIONS: Reformulation of products to meet the targets could result in substantial reductions in cardiovascular disease without changes in dietary behaviors. Policymakers should consider options to strengthen salt reduction policies, including effective systems for monitoring and enforcement.
Seated Saline Suppression Test for Lateralizing Primary Aldosteronism.
Leung AA, Padwal RS, Hundemer GL … +10 more , Venos E, Campbell DJT, Holmes DT, Orton DJ, So CB, Przybojewski SJ, Caughlin CE, Pasieka JL, Rabi DM, Kline GA
Hypertension · 2026 May · PMID 41582811 · Publisher ↗
BACKGROUND: Confirmatory testing to identify lateralizing primary aldosteronism (PA) is of uncertain benefit. METHODS: Blinded clinical trial where patients with high-risk features for PA underwent the seated saline supp...
BACKGROUND: Confirmatory testing to identify lateralizing primary aldosteronism (PA) is of uncertain benefit. METHODS: Blinded clinical trial where patients with high-risk features for PA underwent the seated saline suppression test (SSST). All patients received adrenal vein sampling, where lateralization was defined by an aldosterone/cortisol ratio ≥3:1 comparing the dominant versus the nondominant sides. The primary outcome was the overall diagnostic accuracy of the SSST in identifying lateralizing PA using postinfusion aldosterone concentrations of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) with immunoassay, and ≥162 pmol/L (5.8 ng/dL) with liquid chromatography/tandem mass spectrometry. RESULTS: A total of 160 patients completed the trial. Lateralizing PA was diagnosed in 98 patients (61.3%). The overall diagnostic accuracy of the SSST using an aldosterone cutoff of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) was 64.4% (95% CI, 56.4-71.8) and 67.5% (95% CI, 59.7-74.7), respectively. A positive result was equivocal at the lower cutoff of ≥140 pmol/L (5.0 ng/dL; positive likelihood ratio, 1.1 [95% CI, 1.0-1.3]) and minimally informative at the higher cutoff of ≥280 pmol/L (10.1 ng/dL; positive likelihood ratio, 1.9 [95% CI, 1.3-2.7]). Negative results modestly ruled against lateralization using cutoffs of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL; negative likelihood ratio, 0.3 [95% CI, 0.1-0.9]; and 0.5 [95% CI, 0.3-0.7], respectively). The SSST properties were similar with liquid chromatography/tandem mass spectrometry. CONCLUSIONS: Aldosterone suppression testing is unreliable for anticipating adrenal vein sampling outcomes. The SSST may misinform diagnostic-treatment decisions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04422756.
From French Gastronomy to Cardiovascular Health: Cutting Salt in the Baguette Has Saved Thousands of Lives in France.
Grave C, Carcaillon-Bentata L, Bonaldi C … +2 more , Blacher J, Olié V
Hypertension · 2026 Mar · PMID 41582808 · Publisher ↗
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Efficacy and Safety of Finerenone in Patients With Primary Aldosteronism: A Multicenter Prospective Study.
Li P, Yang F, Lou Y … +10 more , Zhang Z, Du Y, Zhang J, Ren Y, Tong A, Xie Z, Shi B, Liu J, Liu L, Zhu D
Hypertension · 2026 May · PMID 41568520 · Publisher ↗
BACKGROUND: Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist. However, robust evidence about its efficacy and safety in primary aldosteronism is scarce. METHODS: In this prospective, multicenter,...
BACKGROUND: Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist. However, robust evidence about its efficacy and safety in primary aldosteronism is scarce. METHODS: In this prospective, multicenter, single-arm, and exploratory trial, we enrolled adults (aged ≤75 years) with primary aldosteronism, an office blood pressure (BP) ranging from 140 to 180/90 to 120 mm Hg, and an estimated glomerular filtration rate ≥60 mL/min per 1.73 m². Eligible patients received finerenone (20-40 mg/d) treatment for 12 weeks. The primary outcome was the change in daytime systolic BP at 12 weeks. RESULTS: Fifty-seven patients were ultimately treated. Per-protocol analysis revealed that finerenone treatment significantly reduced mean daytime systolic BP (-6.69±1.60 mm Hg; <0.001) and diastolic BP (-4.55±1.06 mm Hg; <0.001) according to ambulatory monitoring. Mean office BP decreased even more substantially (systolic BP, -15.58±1.69 mm Hg; diastolic BP, -8.61±1.02 mm Hg; both <0.001). The mean increase in serum potassium concentration was 0.39±0.05 mmol/L, and 94.5% of patients exhibited a normal concentration after 12 weeks of treatment (versus baseline 61.8%; <0.001). Plasma renin activity increased, and 32.7% of patients exhibited a plasma renin activity concentration ≥1 ng/mL per h. According to the Primary Aldosteronism Medical Treatment Outcome criteria, 29.1% and 20.0% of patients achieved complete biochemical and clinical responses, respectively. Treatment was well tolerated. CONCLUSIONS: This study demonstrated the efficacy and safety of finerenone in the treatment of primary aldosteronism, supporting its use as a potential alternative therapy for the condition. Nevertheless, further prospective and head-to-head randomized controlled trials are essential to establish finerenone as a viable substitute for spironolactone. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06381323.
Association of Clinic Blood Pressure and Out-of-Clinic Blood Pressure Difference With Falls Among Older Adults With Hypertension.
Shimbo D, Bowling CB, Cannavale K … +8 more , Fang C, Harrison TN, Qian L, Muntner P, Schwartz JE, Sim JJ, Wei R, Reynolds K
Hypertension · 2026 Mar · PMID 41568454 · Full text
BACKGROUND: A barrier to intensification of antihypertensive medication among older adults with hypertension is the perceived risk of falls. Blood pressure (BP) measured in the clinic setting is primarily used to decide...
BACKGROUND: A barrier to intensification of antihypertensive medication among older adults with hypertension is the perceived risk of falls. Blood pressure (BP) measured in the clinic setting is primarily used to decide whether antihypertensive medication should be intensified. Scarce data exist on whether a lower out-of-clinic BP relative to in-clinic BP is associated with an increased risk of falls among older adults with hypertension. METHODS: The sample included 630 participants, enrolled from May 2019 to November 2022 from Kaiser Permanente Southern California, who were aged ≥65 years, had hypertension, were taking antihypertensive medication, and had not experienced a serious fall injury since their last clinic visit. The primary exposure was quartiles (Qs) of the difference between clinic systolic BP from the electronic health record and awake systolic BP on ambulatory BP monitoring. The primary outcome was time to the first fall, determined using monthly falls calendars over 12 months of follow-up. RESULTS: The mean age (SD) was 74.6 (6.2) years with 56.5% female. During follow-up, 240 (38.1%) of the 630 participants fell. After adjusting for demographics, clinical characteristics, and geriatric measures, participants in Q4 (7.2-47.7 mm Hg) versus Q1-Q3 (-56.7 to <7.2 mm Hg) of clinic systolic BP from the electronic health record and awake systolic BP did not have an increased fall risk: adjusted hazard ratio, 0.79 (95% CI, 0.57-1.09). CONCLUSIONS: There was no evidence of an association of a lower awake systolic BP on ambulatory BP monitoring relative to clinic systolic BP with an increased risk of falls.
Development and Characterization of a Novel Chronic Thromboembolic Pulmonary Hypertension Rat Model: Identifying Sell-Podxl as Potential Regulators.
Liu J, Hou L, Yang J … +22 more , Xu Z, Zhang H, Niu X, Miao R, Hu Y, Pang W, Liu M, Chang Z, Tian H, Li X, Sun L, Zhang Z, Zhang S, Zhang Y, Zhang Y, Gao Q, Wang D, Xie W, Huang Q, Song W, Yang P, Zhai Z
Hypertension · 2026 Mar · PMID 41568451 · Publisher ↗
BACKGROUND: Chronic thromboembolic pulmonary hypertension is characterized by proximal pulmonary artery obstruction and distal microvasculopathy. However, the mechanisms driving this dual-compartment pulmonary vascular r...
BACKGROUND: Chronic thromboembolic pulmonary hypertension is characterized by proximal pulmonary artery obstruction and distal microvasculopathy. However, the mechanisms driving this dual-compartment pulmonary vascular remodeling remain unclear. METHODS: Male Sprague-Dawley rats were injected with gelatin sponge combined with SU5416 as a secondary insult. Hemodynamics, echocardiography, and pulmonary vascular remodeling were evaluated to investigate the development of chronic thromboembolic pulmonary hypertension. Single-cell RNA sequencing of rat lung tissue was conducted to elucidate the molecular mechanisms underlying pulmonary vascular remodeling. The results were validated by immunofluorescence and cell-based experiments. RESULTS: The optimal size range of gelatin sponge for large pulmonary artery obstruction was 710 to 1000 µm, which synergized with a low dose of SU5416 (10 mg/kg) to induce significant increases in right ventricular systolic pressure and right ventricular hypertrophy at 5 weeks. The model exhibited persistent elastic pulmonary artery obstruction and remodeling, along with significant wall thickening and muscularization of pulmonary microvessels. Single-cell transcriptomic analysis revealed a significant reduction in microvascular endothelial cells and an increase in smooth muscle cells in the chronic thromboembolic pulmonary hypertension rats. , , and were identified as key genes driving aberrant smooth muscle cell proliferation. The (encoding L-selectin)- (encoding PODXL, podocalyxin) ligand-receptor pair was found specifically in diseased rats and mediated immune cell-endothelial cell interactions. L-selectin promoted neutrophil adhesion and dysfunction in pulmonary arterial and microvascular endothelial cells, both of which were reversed by PODXL knockdown. CONCLUSIONS: Our new model recapitulates human chronic thromboembolic pulmonary hypertension pathophysiology and is useful for understanding pulmonary microvasculopathy. Sell-Podxl is a previously unrecognized link between inflammation and vascular remodeling, offering a potential therapeutic target.
Nocturnal Hypertension and Prognosis in Patients of Very Advanced Age.
Fujiwara T, Hoshide S, Kario K
Hypertension · 2026 Mar · PMID 41568439 · Publisher ↗
BACKGROUND: Nocturnal blood pressure (BP) is a better predictor of health outcomes than office or daytime BP. However, the clinical significance of nocturnal hypertension in patients of very advanced age remains unexplor...
BACKGROUND: Nocturnal blood pressure (BP) is a better predictor of health outcomes than office or daytime BP. However, the clinical significance of nocturnal hypertension in patients of very advanced age remains unexplored. We aimed to assess the association between nocturnal hypertension and composite cardiovascular outcomes in this population. METHODS: This was a prospective observational study including Japanese elderly outpatients aged ≥80 years. All patients underwent 24-hour ambulatory BP monitoring at baseline. Nocturnal hypertension was defined as nocturnal systolic BP ≥120 mm Hg or diastolic BP≥70 mm Hg. Daytime hypertension was defined as daytime systolic BP ≥135 mm Hg and diastolic BP ≥85 mm Hg. The association between those BP phenotypes and composite cardiovascular outcomes (including fatal and nonfatal cardiovascular disease and all-cause mortality) was examined using Cox regression analysis. RESULTS: A total of 485 patients were followed for a median of 3.9 years (1734 person-years), during which 72 (14.8%) composite cardiovascular outcomes occurred. The median age (interquartile range) was 82 (81-85) years; 44.7% were male; and 89.3% took antihypertensive medications. Nocturnal hypertension and daytime hypertension were present in 54.2% and 33.6% of patients, respectively. Relative to nocturnal normotension (nocturnal systolic BP <120 mm Hg and diastolic BP <70 mm Hg), nocturnal hypertension was associated with an increased risk of composite cardiovascular outcomes, even after adjustment for daytime BP values (adjusted hazard ratio, 2.15 [95% CI, 1.18-3.93]). Daytime hypertension showed no such association. CONCLUSIONS: Screening for nocturnal hypertension identifies a high-risk group for composite cardiovascular outcomes among patients of very advanced age.
Finerenone Improves Albuminuria via MR-TRPC Signaling in Diabetic Kidney Disease.
Iwakura T, Kidokoro K, Tatsugawa R … +11 more , Hirano A, Kajimoto E, Takasu M, Wada M, Wada Y, Kadoya H, Kishi S, Nagasu H, Cherney DZI, Sasaki T, Kashihara N
Hypertension · 2026 Apr · PMID 41568437 · Publisher ↗
BACKGROUND: Recent studies have confirmed the protective effects of nonsteroidal MR (mineralocorticoid receptor) antagonists in diabetic kidney disease. However, the physiological mechanisms underlying their albuminuria-...
BACKGROUND: Recent studies have confirmed the protective effects of nonsteroidal MR (mineralocorticoid receptor) antagonists in diabetic kidney disease. However, the physiological mechanisms underlying their albuminuria-reducing effects remain incompletely defined. We hypothesized that inhibition of the MR could protect podocytes by limiting excessive calcium influx via TRPC (transient receptor potential canonical) 5, thereby reducing albuminuria. METHODS: We evaluated the effects of the nonsteroidal MR antagonist finerenone on albuminuria, podocyte morphology, and glomerular function in diabetic mice. Reactive oxygen species generation and single-nephron glomerular filtration rate were analyzed using in vivo imaging. Cultured podocytes were used to assess MR-TRPC5 signaling through measurements of Sgk1 (serum- and glucocorticoid-regulated kinase 1) and TRPC5 expression, intracellular calcium, and actin cytoskeletal organization. RESULTS: Finerenone significantly reduced albuminuria, ameliorated podocyte morphological abnormalities, and decreased glomerular reactive oxygen species production in diabetic mice. In cultured podocytes, aldosterone increased Sgk1 and TRPC5 expression, elevated intracellular calcium, and induced actin reorganization; these changes were attenuated by finerenone and by the AC1903 (TRPC5 inhibitor). Activation of MR-TRPC signaling was associated with increased calcium influx and features of podocyte injury. In vivo imaging further indicated that finerenone was associated with lower single-nephron glomerular filtration rate, consistent with an attenuation of glomerular hyperfiltration. CONCLUSIONS: Finerenone is associated with reductions in albuminuria in diabetic kidney disease, together with improvements in podocyte injury indices and glomerular hemodynamics. These benefits may be mediated in part through MR-TRPC5 signaling although additional pathways are likely to contribute.
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